1,4-Dioxane → HCID 86687526, compound

HRID 1473477Notes

Reaction equation

HRID 1473477 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15]([C:25]3[S:26][C:27]([F:30])=[CH:28][N:29]=3)CC3C=CC(OC)=CC=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[N:4][N:3]=1.[CH3:31][O:32][C:33]1[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][C:34]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[F:30][C:27]1[S:26][C:25]([NH:15][S:12]([C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[C:2]([C:34]2[CH:35]=[CH:36][C:37]([C:39]([F:42])([F:41])[F:40])=[CH:38][C:33]=2[O:32][CH3:31])=[N:3][N:4]=[CH:5]3)(=[O:13])=[O:14])=[N:29][CH:28]=1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 86687450HCID 86687450, compound

Product 1

HCID 86687526HCID 86687526, compoundYield 60.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A vial was charged with 1-chloro-N-(5-fluorothiazol-2-yl)-N-(4-methoxybenzyl)phthalazine-6-sulfonamide (Intermediate CCCC) (55.94 mg, 0.120 mmol), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (Combi-Blocks, San Diego, Calif., 31.8 mg, 0.144 mmol), Pd(AmPhos)2Cl2 (4.26 mg, 6.02 μmol), potassium phosphate (77 mg, 0.361 mmol), 1,4-dioxane (451 μl), and water (150 μl). The vial was flushed with Ar (g), then sealed and heated in a microwave reactor for 30 min at 90° C. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The residue was dissolved in DCM (1 mL) and TFA (0.5 mL). After 30 min, the mixture was diluted with MeOH and concentrated, and the crude product was purified by chromatography on silica gel (12-g column, 0 to 7% MeOH/DCM) to give N-(5-fluorothiazol-2-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazine-6-sulfonamide (35.18 mg, 0.073 mmol, 60.4% yield) as a cream-colored solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.88 (s, 1H), 9.96 (s, 1H), 8.76 (d, J=1.9 Hz, 1H), 8.22 (dd, J=1.9, 8.7 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.68 (d, J=7.7 Hz, 1H), 7.60-7.52 (m, 2H), 7.41 (s, 1H), 3.77 (s, 3H); m/z (ESI) 485.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. customsealed
  3. extractionThe mixture was extracted with EtOAc (3×)
  4. concentrationthe combined organic extracts were concentrated
  5. dissolutionThe residue was dissolved in DCM (1 mL)
  6. additionthe mixture was diluted with MeOH
  7. concentrationconcentrated
  8. customthe crude product was purified by chromatography on silica gel (12-g column, 0 to 7% MeOH/DCM)

Sources & evidence

ORD record
ord-d50ed10890cf47fcbd76b9be569990d1
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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